The corneal ulceration (keratomalacia) associated with vitamin A deficiency is a major cause of world blindness, yet its pathogenesis remains uncertain. Experimental and clinical evidence implicates several possible etiologic factors, including injury, inflammation, and infection. Our central hypothesis is that the vitamin A-deficient cornea is predisposed to infection by microbial agents as well as to destruction by an enhanced inflammatory response following minor environmental trauma (eg, exposure or abrasion) of the corneal epithelium. The long-term objective of this proposal is to learn the interrelationship between vitamin A status and the ocular response to injury and infection in order to better understand the basis for this disease and its treatment. Using a well-characterized nutritional model, the vitamin A-deficient rat, we play to combine clinical, biochemical, and morphologic techniques both in vitro and in vivo to study the corneal responses to epithelial and stromal trauma, to acute inflammatory cells, and to specified bacterial pathogens. Specifically, we propose: (1) to determine in an organ culture system both the interaction between the vitamin A-deficient cornea and polymorphonuclear neutrophils (PMNs) with respect to epithelial wound healing and collagenolytic and other enzyme activities, plus the interrelations of fibronectin, epithelial wound healing, and vitamin A. (2) to examine the in vitro effect of retinoids and other pharmacologic agents (specifically theophylline, cholera toxin, dexamethasone, and indomethacin) capable of altering PMN and collagenase activity, and (3) to characterize the susceptibility of the vitamin A-deficient cornea to bacterial infection in vivo with respect to specific microorganisms, epithelial and/or stromal injury, and the effect of antibiotics and retinoic acid therapy.